1. Field of the Invention
The present invention relates to a novel formulation containing (R)-1-(3-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3- piperidinecarboxylic acid or a pharmaceutically acceptable salt thereof, and to its use in the treatment and/or prophylaxis of certain disorders.
2. Description of the Related Art
WO 95/18793 and WO 97/22338 discloses inter alia (R)-1-(3-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3- piperidinecarboxylic acid or a pharmaceutically acceptable salt thereof, and the use of the compound to treat all painful, hyperalgesic and/or inflammatory conditions in which C-fibres play a pathophysiological role by eliciting neurogenic pain or inflammation. Further, it has been demonstrated that (R)-1-(3-(10,11 -Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3-piperidinecarbo xylic acid or a pharmaceutically acceptable salt thereof, is useful in reducing blood glucose and/or inhibiting the secretion, circulation or effect of insulin antagonizing peptides like CGRP or amylin.
The formulations containing (R)-1-(3-(10,11 -Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3-piperidinecarbo xylic acid or a pharmaceutically acceptable salt thereof, as suggested in WO 95/18793 and WO 97/22338, relate to formulations which are prepared by conventional techniques. The formulations mentioned appear in conventional forms, for example capsules, tablets, aerosols, solutions, suspensions or topical applications.
The half-life for (R)-1-(3-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3- piperidinecarboxylic acid is relatively short, and in order to control the release of the compound in such a manner that an effective concentration in the blood can be maintained over an extended period of time but also that the drug concentration in the blood remains relatively constant over an extended period of time, there exists a need for a modified release formulation for (R)-1-(3-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3- piperidinecarboxylic acid.
The use of modified release formulations will furthermore improve patient compliance as it reduces the numbers of dosages to be taken per day.
Thus one object of the present invention is to provide modified release formulations containing (R)-1-(3-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3- piperidinecarboxylic acid or a pharmaceutically acceptable salt thereof to reduce the fluctuations in plasma concentrations and thereby reduce any inconvenience therefrom.
To reduce plasma fluctuations it is necessary to provide modified release formulations with zero-order drug release. However, zero-order drug release is difficult to obtain for modified release products, especially for matrix tablets comprising hydroxypropylmethylcellulose, which is a polymer often used within modified release formulations.